Investigations into the DNA-binding mode of doxorubicinone.

Cancer treatment is one of the major challenges facing the modern biomedical profession. Development of new small-molecule chemotherapeutics requires an understanding of the mechanism of action for these treatments, as well as the structure-activity relationship. Study of the well-known DNA-intercalating agent, doxorubicin, and its aglycone, doxorubicinone, was undertaken using a variety of spectroscopic and calorimetric techniques. It was found that, despite conservation of the planar, aromatic portion of doxorubicin, the agylcone does not intercalate; it instead likely binds to the DNA minor-groove.

[1]  Katherine E. Buxton,et al.  Investigating the impacts of DNA binding mode and sequence on thermodynamic quantities and water exchange values for two small molecule drugs. , 2016, Biophysical chemistry.

[2]  Swarup Roy,et al.  Report of Interaction Between Calf Thymus DNA and Pyrimidine-AnnulatedSpiro-Dihydrofuran , 2016 .

[3]  S. Fujii,et al.  Thermodynamics and kinetic studies in the binding interaction of cyclic naphthalene diimide derivatives with double stranded DNAs. , 2015, Bioorganic & medicinal chemistry.

[4]  M. Giustini,et al.  Interaction of doxorubicin with polynucleotides. A spectroscopic study. , 2014, Biochemistry.

[5]  A. Ramu,et al.  Evaluation of DNA Binding, Cleavage, and Cytotoxic Activity of Cu(II), Co(II), and Ni(II) Schiff Base Complexes of 1-Phenylindoline-2,3-dione with Isonicotinohydrazide , 2014, Bioinorganic chemistry and applications.

[6]  B. García,et al.  New insights into the mechanism of the DNA/doxorubicin interaction. , 2014, The journal of physical chemistry. B.

[7]  D. Arya,et al.  Natural product DNA major groove binders. , 2012, Natural product reports.

[8]  Jim A. Thomas,et al.  Photoactive Ru(II) -polypyridyl complexes that display sequence selectivity and high-affinity binding to duplex DNA through groove binding. , 2011, Chemistry.

[9]  Anuradha,et al.  Osmolyte changes the binding affinity and mode of interaction of minor groove binder hoechst 33258 with calf thymus DNA. , 2010, Chemical & pharmaceutical bulletin.

[10]  S. Burgmayer,et al.  DNA binding by Ru(II)–bis(bipyridine)–pteridinyl complexes , 2008, JBIC Journal of Biological Inorganic Chemistry.

[11]  F. Keene,et al.  DNA affinity binding studies using a fluorescent dye displacement technique: the dichotomy of the binding site , 2007, JBIC Journal of Biological Inorganic Chemistry.

[12]  J. Chaires,et al.  A thermodynamic signature for drug-DNA binding mode. , 2006, Archives of biochemistry and biophysics.

[13]  D. Rau,et al.  Preferential hydration of DNA: the magnitude and distance dependence of alcohol and polyol interactions. , 2006, Biophysical journal.

[14]  T. Herman,et al.  Enhanced topoisomerase II targeting by annamycin and related 4-demethoxy anthracycline analogues. , 2004, Molecular cancer therapeutics.

[15]  R. L. Coffee,et al.  From triplex to B-form duplex stabilization: reversal of target selectivity by aminoglycoside dimers. , 2004, Bioorganic & medicinal chemistry letters.

[16]  G. Minotti,et al.  Doxorubicin-dependent reduction of ferrylmyoglobin and inhibition of lipid peroxidation: Implications for cardiotoxicity of anticancer anthracyclines , 2002 .

[17]  A. Rodger,et al.  Aryl substituted ruthenium bis-terpyridine complexes: intercalation and groove binding with DNA. , 2002, Journal of inorganic biochemistry.

[18]  J. Chaires,et al.  Hydration changes for DNA intercalation reactions. , 2001, Journal of the American Chemical Society.

[19]  C. Hutchinson,et al.  Doxorubicin Overproduction in Streptomyces peucetius: Cloning and Characterization of the dnrU Ketoreductase anddnrV Genes and the doxA Cytochrome P-450 Hydroxylase Gene , 1999, Journal of bacteriology.

[20]  B. Nordén,et al.  DNA Binding Geometries of Ruthenium(II) Complexes with 1,10-Phenanthroline and 2,2‘-Bipyridine Ligands Studied with Linear Dichroism Spectroscopy. Borderline Cases of Intercalation , 1998 .

[21]  R. Pagni Circular Dichroism and Linear Dichroism (Rodger, Alison; Norden, Bengt) , 1998 .

[22]  A. Garnier-Suillerot,et al.  Comparison of the interaction of doxorubicin, daunorubicin, idarubicin and idarubicinol with large unilamellar vesicles. Circular dichroism study. , 1998, Biochimica et biophysica acta.

[23]  B. Jollès,et al.  Comparison of DNA sequence selectivity of anthracycline antibiotics and their 3'-hydroxylated analogs. , 1996, Chemico-biological interactions.

[24]  J. Chaires,et al.  Parsing the free energy of anthracycline antibiotic binding to DNA. , 1996, Biochemistry.

[25]  J. Chaires,et al.  Criteria for the mode of binding of DNA binding agents. , 1995, Bioorganic & medicinal chemistry.

[26]  D. Rau,et al.  The osmotic sensitivity of netropsin analogue binding to DNA , 1995, Biopolymers.

[27]  Y. Pommier,et al.  Hydroxyrubicin, a deaminated derivative of doxorubicin, inhibits mammalian DNA topoisomerase II and partially circumvents multidrug resistance , 1994, International journal of cancer.

[28]  J. Chaires,et al.  Neither delta- nor lambda-tris(phenanthroline)ruthenium(II) binds to DNA by classical intercalation. , 1992, Biochemistry.

[29]  V. Rizzo,et al.  Kinetic studies of anthracycline-DNA interaction by fluorescence stopped flow confirm a complex association mechanism. , 1989, Biochemistry.

[30]  H. Blöcker,et al.  Predicting DNA duplex stability from the base sequence. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[31]  W. Förster,et al.  Interaction of anthracycline antibiotics with biopolymers: 9. Comparative study of the interaction kinetics of daunomycin, adriamycin and iremycin with DNA , 1984 .

[32]  E. Stutter,et al.  Interaction of anthracycline antibiotics with biopolymers: 7. Equilibrium binding studies on the interaction of iremycin and DNA , 1983 .

[33]  D. Henry,et al.  Synthetic approaches to adriamycin. 2. Degradation of daunorubicin to a nonasymmetric tetracyclic ketone and refunctionalization of the A ring to adriamycin. , 1977, The Journal of organic chemistry.

[34]  T. Lohman,et al.  Ion effects on ligand-nucleic acid interactions. , 1976, Journal of molecular biology.

[35]  H. J. Li,et al.  Relaxation studies of the proflavine-DNA complex: the kinetics of an intercalation reaction. , 1969, Journal of molecular biology.

[36]  G. W. Lehman,et al.  Melting of DNA. , 1968, The Journal of chemical physics.

[37]  M. Waring,et al.  Complex formation between ethidium bromide and nucleic acids. , 1965, Journal of molecular biology.

[38]  V. Subramanian,et al.  Synthesis, characterization and DNA-binding properties of rac-[Ru(5,6-dmp)2(dppz)]2+--enantiopreferential DNA binding and co-ligand promoted exciton coupling. , 2006, Journal of inorganic biochemistry.

[39]  T. Lohman,et al.  Thermodynamics of ligand-nucleic acid interactions. , 1992, Methods in enzymology.